[unreadable] Crohn's disease is a chronic relapsing and remitting condition causing inflammation of the bowel. The major symptoms of Crohn's disease include abdominal pain, diarrhea, gastrointestinal bleeding, malabsorption, and weight loss. The etiology of Crohn's disease is unknown. Biopsies obtained from the bowel in subjects with Crohn's disease reveal inflammatory cells suggesting that the bowel is either reacting immunologically to a stimulus or the endogenous immune system of the gastrointestinal track is off balance. The treatment of IBD always has been directed toward inflammation. Drugs (e.g., steroids or azathioprine) are used to decrease the inflammatory response in the bowel by suppressing the host immune system. Most recently, anti-tumor necrosis factor (TNF) strategies for Crohn's disease have developed, and a new era of treatment with specific immunotherapy has been developed. These medications are chimeric antibodies that are extremely expensive and have potential side effects. Our research in the basic science laboratory has involved studying the endogenous opioid systems (i.e., enkephalins and endorphins, and opioid receptors), and their role on growth and wound healing. We have shown in a mouse with chemically-induced colitis that naltrexone significantly decreases inflammation of the bowel and improves the inflammatory index. A pilot study tested the clinical response to oral naltrexone in subjects with active Crohn's disease and found significant improvement in the Crohn's Disease Activity Index (CDAI) as well as endoscopic reversal of inflammation. It is hypothesized that oral naltrexone will improve inflammation of the bowel by increasing endogenous enkephalin levels in subjects with active Crohn's disease. In order to test this hypothesis, 40 subjects with active Crohn's disease will be randomized to receive either oral naltrexone (4.5 mg) or placebo daily for 3 months. Subjects' response will be monitored by the CDAI scores, endoscopy, histology, and quality of life surveys. After 3 months of therapy all subjects will be treated in an open-labeled fashion to test the longevity of response and determine if 6 months of therapy is better than 3 months. Durability of response will be evaluated in a 1-month follow-up. This trial is based upon novel innovative preclinical and clinical data and may lead to a larger multi-center trial in the future. [unreadable] [unreadable] [unreadable]